title: The rs8099917 polymorphism, when determined by a suitable genotyping method, is a better predictor for response to pegylated alpha interferon/ribavirin therapy in Japanese patients than other single nucleotide polymorphisms associated with interleukin-28B.
abstract: We focused on determining the most accurate and convenient genotyping methods and most appropriate single nucleotide polymorphism (SNP) among four such polymorphisms associated with interleukin-28B (IL-28B) in order to design tailor-made therapy for patients with chronic hepatitis C virus (HCV) patients. First, five different methods (direct sequencing, high-resolution melting analysis [HRM], hybridization probe [HP], the InvaderPlus assay [Invader], and the TaqMan SNP genotyping assay [TaqMan]) were developed for genotyping four SNPs (rs11881222, rs8103142, rs8099917, and rs12979860) associated with IL-28B, and their accuracies were compared for 292 Japanese patients. Next, the four SNPs associated with IL-28B were genotyped by Invader for 416 additional Japanese patients, and the response to pegylated interferon/ribavirin (PEG-IFN/RBV) treatment was evaluated when the four SNPs were not in linkage disequilibrium (LD). HRM failed to genotype one of the four SNPs in five patients. In 2 of 287 patients, the results of genotyping rs8099917 by direct sequencing differed from the results of the other three methods. The HP, TaqMan, and Invader methods were accurate for determination of the SNPs associated with IL-28B. In 10 of the 708 (1.4%) patients, the four SNPs were not in LD. Eight of nine (88.9%) patients whose rs8099917 was homozygous for the major allele were virological responders, even though one or more of the other SNPs were heterozygous. The HP, TaqMan, and Invader methods were suitable to determine the SNPs associated with IL-28B. The rs8099917 polymorphism should be the best predictor for the response to the PEG-IFN/RBV treatment among Japanese chronic hepatitis C patients.
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Ito
authors.forename: Katsuya
authors.initials: K
authors.lastname: Higami
authors.forename: Naohiko
authors.initials: N
authors.lastname: Masaki
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Motokazu
authors.initials: M
authors.lastname: Mukaide
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Saito
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Yo
authors.initials: Y
authors.lastname: Sato
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Imamura
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Murata
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nomura
authors.forename: Shuhei
authors.initials: S
authors.lastname: Hige
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Adachi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.forename: Etsuro
authors.initials: E
authors.lastname: Orito
authors.forename: Satomi
authors.initials: S
authors.lastname: Kani
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D044466:Asian People; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda